This project covers studies aimed at expanding our understanding of the various genetically specified mechanisms involved in determining sensitivity and resistance of inbred mice to murine leukemia virus (MuLV) infection and disease induction. At present two major areas are under study, one involving exogenous infection of mice by the replication defective MAIDS MuLV as well as replication competent helper MuLVs, and the second studying the hematopoietic tumors developing spontaneously in NFS v-congenic mice - mice of similar virus negative, low spontaneous lymphoma background that carry germ-line integrations of ecotropic MuLVs derived from the high virus, high thymic lymphoma incidence AKR and C58 strains. In the first area of study, in which both Class I and Class II MHC effects on sensitivity and resistance to MAIDS have been described previously, the effects of unmapped genes outside the MHC complex that modify disease and may or may not affect helper virus replication are being studied. Having analyzed a number of strains for polymorphisms in disease induction and helper virus replication, we are now testing crosses of sensitive and resistant pairs [B10.RIII and RIIIS (both H-2r), C57L and 129 (both H2b), C57BL and 129 (both H-2b), and SWXL-4 and SWR (H-2q)] at various times post-inoculation for presence and degree of disease, replication of helper virus, and integration and mRNA expression of defective and helper virus. Attempts will be made to map non-H-2 genes affecting disease induction by use of microsatellite DNA PCR analysis. In the second area of effort, a large series of spontaneous v-congenic T and B cell lymphomas has been characterized for microscopic morphology, by immunological phenotyping, and for alterations in immunoglobulin and T cell receptor genes. In addition to relating individual tumors to lineage origin and clarifying the classification of mouse lymphomas, two B cell lymphomas - immunocytoma and marginal zone lymphoma - previously undescribed in mice have been characterized.